CA is a rare monoclonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in the heart. Due to the insufficient understanding of the disease, delay in diagnosis, multiple organ involvement, treatment methods, and so on, the average survival time of patients is short.[2]
Retrospective analysis showed that ischemic stroke was a complication of CA, is closely associated with poor prognosis and increased all-cause mortality, some patients presented with cerebral infarction as the first symptom, while a few patients presented with recurrent cerebral infarction.[3] A cohort study of 406 CA patients revealed a 7.6% incidence of arterial thrombotic events, mostly cerebrovascular events, with the CHADS2-VAsc score ≥ 3 being the only predictive factor for thrombotic events in Cox analysis, especially in patients with sinus rhythm. [4] Studies by Park et al. have shown that for newly diagnosed patients with AL-CA, a greater free light chain difference and β2 microglobulin levels were risk factors for thromboembolic events. [5] Ischemic stroke is closely related to intracardiac thrombosis caused by atrial arrhythmia and atrial mechanical dysfunction caused by amyloid deposition. [1, 3, 4] Non-cardiac factors such as nephrotic syndrome-induced loss of natural anticoagulant factors, increased synthesis of procoagulant factors, decreased patient mobility, and therapeutic drugs all increased the risk of thrombotic events in CA. TTE, TEE, and CMR are not only a part of CA diagnostic examination, but are also an important means of thrombus event evaluation.[6] Enhanced systematic assessment and close monitoring of thrombus events in high-risk patients may help improve outcomes.
Anticoagulant therapy reduces the risk of intracardiac thrombosis associated with AF and left ventricular diastolic dysfunction in patients with CA. [7] The incidence of AF in AL-CA can reach 56%, Consensus states that anticoagulation therapy is recommended for patients with AF regardless of the CHA2DS2-VASc risk score. [8, 9] Warfarin's efficacy varies significantly between patients and necessitates close monitoring of INR, which is challenging to apply in CA patients with bleeding risk. In patients with nonvalvular heart disease, where the risk of cerebral hemorrhage is higher with traditional anticoagulants such as warfarin, new oral anticoagulants (NOACs) such as rivaroxaban and dabigatran reduce the risk of stroke and bleeding. Specific reversal agents can reverse the anticoagulant effect of NOACs when severe post-anticoagulant bleeding occurs, but they are expensive and may increase the risk of thrombotic complications. [10] Both warfarin and NOACs may interact with drugs used to treat CA, and the choice of different anticoagulants for this specific population needs more exploration.
A retrospective observational cohort study of 72 patients with ATTR-CA complicated with AF found that ablation was associated with a reduction in the hospitalization for AF or heart failure and improved survival. [11] During the follow-up, nearly half of the patients had no recurrent arrhythmia, and the benefit was the greatest when ablation was performed earlier in the disease course. Another retrospective analysis included 26 patients with CA complicated with AF (AL-CA 7, ATTR-CA 19), catheter ablation treatment improved arrhythmia but had uncertain effect on long-term prognosis such as survival rate. [12] A case of AL-CA with atrial tachycardia survived well after 5 years of radiofrequency ablation, particularly, the patient experienced sinus arrest and was implanted with a single ventricular pacemaker, [13] and conduction dysfunction is another possible complication of CA. Whether the contribution of radiofrequency ablation in the treatment of CA complicated with arrhythmia is limited to the elimination of symptoms or the improvement of long-term prognosis still needs more cases to explore. Thrombolysis within the effective time window is an effective means of treating stroke and reducing the sequelae of the nervous system. During the review, it was discovered that two patients received thrombolytic therapy and survived the follow-up period. However, the long-term prognosis remains unknown. [14, 15] Thrombolytic therapy significantly increased the risk of bleeding in patients with CA, and its benefits remain to be studied.
Marques P et al. described a patient with AL amyloidosis who had an ischemic stroke as the first symptom and intracranial haemorrhage as the disease progressed. The patient had AF, left auricular thrombosis, and nephrotic syndrome. After the intracranial haemorrhage was stabilized, warfarin was given as anticoagulant therapy, and amyloidosis was also treated, but she died 2 months later of a second ischemic stroke. [16] Despite the fact that our patient had no AF and atrial or ventricular thrombosis, or other high risk factors for cardiovascular and cerebrovascular events, she still experienced multiple cerebral infarctions with concurrent intracerebral microbleeding. No anticoagulant or thrombolytic treatment was given when the patient experienced neurological symptoms. No CMR examination was performed again during treatment follow-up, there may be hidden thrombi that cannot be detected by echocardiography or the thrombus may have been dislodged. Although multiple electrocardiogram and dynamic electrocardiogram examinations were performed during the course of the disease, there may be paroxysmal AF that was not captured. Clinicians should perform TTE, TEE, and CMR in patients with a definite diagnosis of CA to fully assess and monitor thrombosis. CA combined with AF, active anticoagulation therapy has positive significance in preventing atrial or ventricular thrombosis and cardiogenic cerebral embolism. Based on the bleeding tendency of the disease, more clinical data are needed to support the complete assessment of bleeding risk (especially cerebral haemorrhage) before anticoagulant treatment and whether there are differences among different drugs (e.g. heparin, low molecular weight heparin, warfarin, rivaroxaban, and dabigatran). In the absence of capture of AF and atrial or ventricular wall thrombosis, ischemic and haemorrhagic stroke coexist, and it is worth exploring how clinicians decide on anticoagulant treatment.